SCIENCE: Scripps Research Institute Gets $77M for AIDS vaccine center

The National Institutes of Health has awarded The Scripps Research Institute a grant expected to total more than $77 million for an AIDS vaccine center. This represents the only such center funded on the West Coast by the federal agency.

The seven-year grant, announced Wednesday, establishes the Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, or CHAVI-ID. It will study how to use the body's immune system to fight HIV, the virus that causes AIDS. Research will examine ways to help those with HIV resist the virus, as well as to prevent infection. Scripps will get $11 million annually over seven years, and possibly more.

Jobs will come with the grant as the new center ramps up hiring at Scripps and other research centers that are participating, said
Dennis Burton
, a Scripps professor in the department of Immunology and Microbial Science.

Burton heads the new vaccine center. Its leadership includes researchers at the La Jolla Institute for Allergy & Immunology and the Sanford Burnham Medical Research Institute, both close by Scripps in La Jolla. In addition, the leaders are drawn from several other institutions across the country, and the University of Oxford in England.

Duke University in Durham, N.C., got a similar grant for its own CHAVI-ID center. In 2005, Duke
received
a much larger federal grant, $300 million, for the same purpose.

"Last year, they announced a re-competition, and we applied, and this time they awarded two centers," Burton said.

Developing an AIDS vaccine would be a tremendous success, because the disease has thwarted decades of attempts. The Immune Response Corp., a now-defunct biotech company in Carlsbad, tried for years to develop a vaccine, with almost nothing to show for its efforts. The company, which had been rechristened
Orchestra Therapeutics
, filed for Chapter 7 bankruptcy in 2008.

Meanwhile, the number of people living with HIV and AIDS worldwide continues to grow. That's in part because better drugs are keeping people alive longer, but also because more people continue to get infected. From about 10 million in 1991, the population of those with HIV grew to 34 million by the end of 2010. Of those, 2.7 million were newly infected. And 1.8 million died, many in impoverished countries where the newer HIV drugs aren't readily available.

Neutralizing power

Burton and colleagues have identified a promising approach to a vaccine with what are called "broadly neutralizing" antibodies effective against many strains of HIV. They are studying this approach under the nonprofit
International AIDS Vaccine Initiative
, or IAVI. In 2009, the initiative
established
the IAVI Neutralizing Antibody Center at The Scripps Research Institute.

Like the flu, HIV appears in different varieties, and mutates extremely rapidly. So when the immune system makes antibodies that target HIV, the virus changes enough so that the antibodies stop working. And the virus also infects white blood cells called T cells, necessary for a strong immune response. Eventually, the immune system gives up, and AIDS appears.

However, certain individuals have lived long with HIV in good health, and produce unusually effective antibodies. These are the broadly neutralizing antibodies Burton and other researchers have discovered in the past three years. They are studying how to make the antibodies even more effective.

Burton's goal is to develop a preventive vaccine. He described the process as "working backward" from the desired goal to find the trigger that produces the antibodies they already know exist. Ordinarily, vaccines are produced by first injecting some part of the microbe, or a weakened version, to prompt the body to produce the required antibodies.

Tapping new knowledge

"We have the antibodies, so we know what our target is," he said. "The big challenge for us is to produce these sorts of antibodies by vaccination."

Newly acquired knowledge about the immune system can help in the effort, said
Shane Crotty
, a La Jolla Institute researcher participating with Burton in the vaccine center.

Crotty is contributing his immunological expertise to the effort, especially his understanding of antibody-producing cells.

Vaccines today are mainly produced by techniques established decades ago, said Crotty, an associate professor in the La Jolla Institute's vaccine discovery division. While the methods work much of the time, the old techniques have proven to be inadequate for HIV.

Research has shown that a certain kind of T cell, called a
follicular helper CD4 T cell
, plays a key role in antibody production, Crotty said. The more of these cells, the more antibodies are produced.

Traditional measures of immune system function don't measure the follicular helper cell count, Crotty said. For an HIV vaccine, the activity of these cells needs to be monitored.

"Not only are they necessary for an antibody response, but they seem to be a truly central player," Crotty said. "It makes sense to understand those cells, and how to generate more of them, if you want to make a good antibody."

Long road ahead

Burton said that while there's increasing cause for optimism, he's not expecting quick success with vaccines based on the broadly neutralizing antibodies. Incremental progress is more likely.

Some potential vaccines are already in the works.

"We do have candidates that I would describe as early candidates," Burton said. "They're unlikely to be home runs, but we may find some partial success from these and then be able to tweak the vaccine candidates to become better and better. That's our hope."